Center News Magazine: Toward the Next Generation of Medical Imaging

Friday, May 1, 2009

Michelle Bradbury

Researchers Will Explore “C Dots” for Tumor Detection and Treatment

What if a tumor could be lit up by a fluorescent imaging agent, or probe, that is safe, biologically stable, and bright enough for a physician to detect it noninvasively, maybe even with a handheld optical device?

According to Michelle S. Bradbury, an Memorial Sloan Kettering Cancer Center clinician-scientist who specializes in molecular imaging and neuroradiology, such fluorescent probes would have wide applications in detecting and treating cancer. For instance, they might help surgeons to define tumor margins during surgery or detect cancer spread. “It sounds simple conceptually,” she said, “but no optical probes that meet all the necessary requirements for use in the clinic are yet available.” Currently quantum dots, a type of nanoparticle, are used extensively as probes in the laboratory, but their toxicity makes them unsuitable for medical purposes.

Recent studies in mice led by Dr. Bradbury showed that a new generation of nanoparticles called “C dots” might be used for imaging tumors in patients. About one-thousandth the size of a red bloodcell, C dots are small enough to be transported in the blood across the body’s tissues and excreted efficiently through the urine. “C dots have been developed and optimized for biomedical applications in the laboratory of my collaborator, Uli Wiesner [a professor of materials science and engineering at Cornell University],” explained Dr. Bradbury. “Their unique properties and safety afford us the opportunity to reach a new level of tumor diagnosis and treatment.” The findings were published in the January issue of Nano Letters. [PubMed Abstract]

Each C dot is a shell of silica encapsulating molecules that emit long-wavelength light, which easily penetrates tissues. The shell enhances the brightness and stability of these molecules, and is also what makes the C dot biologically safe. “Silica is found in some of the oldest single-cell organisms on this planet,” said Dr. Wiesner. “Had silica not been a biocompatible, nontoxic material, evolution would have eliminated it a long time ago.” To further optimize C dots for medical applications, his team coated them with a polymer that prevents them from clumping or being recognized by the body as a foreign substance.

Graphic representation of a C dot, a nanoparticle made of silica with fluorescent molecules (Cy5) at its core. C dots could offer a safe way to light up tumors and will be explored for medical imaging applications at Memorial Sloan Kettering.

“To the immune system, the particles look like tiny water droplets, so they are free to circulate in the blood until they reach their destination,” explained Oula Penate-Medina, a nanochemist at Memorial Sloan Kettering. A co-author of the study, he labeled the C-dot surface with radioactive molecules. The C dots could then be tracked using two different imaging technologies as they traveled through a mouse’s body: by observing their fluorescence emission using an optical scanner, and by detecting their radioactive signal through positron emission tomography (PET) imaging. “The dual imaging modality allows us to validate what we are observing using fluorescence imaging,” Dr. Bradbury explained.

To test if C dots could be used for tumor targeting, the researchers have tagged them with a protein fragment called RGD, which binds to a protein abundant on cells lining tumor blood vessels. When this probe is injected into a mouse model of human melanoma, it binds to tumors within an hour and can be retained there for several days. In the future, C dots could be tailored to bind specifically to certain tumor types, or even to an individual patient’s tumor. They could then be used to deliver drugs or radioactive molecules to tumors.

“This project has launched a multidisciplinary effort here at Memorial Sloan Kettering. We are grateful to Hedvig Hricak [Chair of the Department of Radiology] for promoting initiatives in applied nanotechnology research and to Steven Larson [Chief of Memorial Sloan Kettering’s Nuclear Medicine Service] for his expertise in developing radiolabeled probes for use in patients,” said Dr. Bradbury. “We are also working with Snehal Patel, a head and neck surgeon, and Ricardo Toledo-Crow, manager of our Research Engineering Laboratory, to bring C dots into the clinic and to build optical instrumentation.”

“Our ultimate goal is to develop C dots for a range of oncology applications, such as minimally invasive surgical procedures or image-guided patient assessments,” Dr. Bradbury added. “Memorial Sloan Kettering is an ideal place for this effort. Not only do we have all the resources and knowledge it takes to bring a discovery from the laboratory into the clinic, we also have the in-house competence for developing new instrumentation. With all these assets, we are likely to see a new generation of medical imaging tools in our clinics within the next five years.”

Other investigators involved in the study were Andrew A. Burns and Erik Herz of Cornell University; Miriam Benezra and Jelena Vider of Memorial Sloan Kettering; and researchers at Hybrid Silica Technologies, Inc.

blood (blud)

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

diagnosis (DY-ug-NOH-sis)

The process of identifying a disease, such as cancer, from its signs and symptoms.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

foreign (FOR-in)

In medicine, foreign describes something that comes from outside the body. A foreign substance in the body’s tissues, such as a bacterium or virus, may be recognized by the immune system as not belonging to the body. This causes an immune response. Other foreign substances in the body, such as artificial joints, are designed to not cause an immune response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

imaging (IH-muh-jing)

In medicine, a process that makes pictures of areas inside the body. Imaging uses methods such as x-rays (high-energy radiation), ultrasound (high-energy sound waves), and radio waves.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immune system (ih-MYOON SIS-tem)

The complex group of organs and cells that defends the body against infections and other diseases.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

medicine (MEH-dih-sin)

Refers to the practices and procedures used for the prevention, treatment, or relief of symptoms of a diseases or abnormal conditions. This term may also refer to a legal drug used for the same purpose.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

modality (moh-DA-lih-tee)

A method of treatment. For example, surgery and chemotherapy are treatment modalities.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

mouse model (... MAH-dul)

The use of special strains of mice to study a human disease or condition, and how to prevent and treat it.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

multidisciplinary (MUL-tee-DIH-sih-plih-NAYR-ee)

In medicine, a term used to describe a treatment planning approach or team that includes a number of doctors and other health care professionals who are experts in different specialties (disciplines). In cancer treatment, the primary disciplines are medical oncology (treatment with drugs), surgical oncology (treatment with surgery), and radiation oncology (treatment with radiation).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

nanoparticle (NA-noh-PAR-tih-kul)

A particle of that is smaller than 100 nanometers (one-billionth of a meter). In medicine, nanoparticles can be used to carry antibodies, drugs, imaging agents, or other substances to certain parts of the body. Nanoparticles are being studied in the detection, diagnosis, and treatment of cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

nanotechnology (NA-noh-tek-NAH-luh-jee)

The field of research that deals with the engineering and creation of things from materials that are less than 100 nanometers (one-billionth of a meter) in size, especially single atoms or molecules. Nanotechnology is being studied in the detection, diagnosis, and treatment of cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

nontoxic (non-TOK-sik)

Not harmful or destructive.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

oncology (on-KAH-loh-jee)

The study of cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

physician (fih-ZIH-shun)

Medical doctor.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

polymer (PAH-lih-mer)

A molecule made up of small identical molecules called monomers. The monomers are joined together in a repeating pattern.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

protein (PROH-teen)

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

radioactive (RAY-dee-oh-AK-tiv)

Giving off radiation.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

radiolabeled (RAY-dee-oh-LAY-buld)

Any compound that has been joined with a radioactive substance.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

scanner (SKA-ner)

In medicine, an instrument that takes pictures of the inside of the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

surgeon (SER-jun)

A doctor who removes or repairs a part of the body by operating on the patient.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

surgery (SER-juh-ree)

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

tomography (toh-MAH-gruh-fee)

A series of detailed pictures of areas inside the body. The pictures are created by a computer linked to an x-ray machine.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

toxicity (tok-SIH-sih-tee)

The extent to which something is poisonous or harmful.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

tumor (TOO-mer)

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

urine (YOOR-in)

Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)